Age Tertiles Research Articles

The impact of pulmonary fibrosis on cardiac function in chronic obstructive pulmonary disease

Abstract Background Emerging evidence indicates the coexistence pulmonary fibrosis and emphysema in patients with Chronic Obstructive Pulmonary Disease (COPD). The effect of pulmonary fibrosis on cardiac structure and function in COPD patients remains unclear. Purpose This study aimed to examine the association between the degree of pulmonary fibrosis identified on Computed Tomographic (CT) imaging and echocardiographic measures of cardiac structure and function in individuals with COPD. Methods The study included 456 individuals with COPD, participating in a large prospective cohort study. Patients with available CT scans and echocardiograms were included. Local histogram-based assessments of lung density were utilized to determine the percentage of fibrosis. Fibrosis was defined based on the CT attenuation within the range of -600 and -250 Hounsfield units. The association between percent fibrosis and measures of cardiac structure and function were investigated by univariable and multivariable linear regression models. Multivariable adjustments included age, sex, body mass index (BMI), and smoking. In addition, restricted cubic splines were generated to visually present the relationship between the percentage of fibrosis and specific echocardiographic parameters. Results The mean age was 71 (± 8 years), 48% were female, and the median BMI was 27 kg/m2 (IQR: 22; 30kg/m2). The mean forced expiratory volume in 1 second as a percentage of the predicted value (FEV1pp) was 47% (±18%). The mean forced vital capacity of predicted value was 71% (± 19%). The median percentage of fibrosis in the cohort was 4.9% (IQR: 3.9; 6.0%). Patients were stratified into tertiles based upon fibrosis percentage. BMI, frequency of diabetes, and FEV1pp were increasingly positively associated with fibrosis. Furthermore, significant trends for echocardiographic measures found that the patients with the most extensive fibrosis were seen to have impaired left ventricular (LV) ejection fraction (LVEF), lower absolute global longitudinal strain (GLS), increased left atrial (LA) volume index (LAVi), and higher LV mass as compared to those with less significant fibrosis. There were no significant differences between tertiles of fibrosis and age or sex. In univariable linear regression, significant inverse associations between the percentage of fibrosis, LVEF, GLS, and tricuspid annular plane systolic excursion (TAPSE) were seen (Table). For LV mass index and LAVi, significant direct associations were found (Table). After adjusting for potential confounding factors, only GLS and LAVi remained associated with pulmonary fibrosis (Figure). Conclusion This study found that GLS and LA volume were significantly associated with the degree of pulmonary fibrosis, even after adjusting for confounding variables. This may suggest that fibrosis is primarily linked with impaired left-sided measures of cardiac structure and function.Linear Regression ModelsCubic Spline Curves

Pulse Pressure and Cardiovascular and Kidney Outcomes by Age in the Chronic Renal Insufficiency Cohort (CRIC).

Wide pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to kidney failure. PP naturally widens with age, but it is unclear whether the risks associated with greater PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with (i) atherosclerotic cardiovascular disease (ASCVD) events or death and (ii) a 50% reduction in estimated glomerular filtration rate or kidney failure in the chronic renal insufficiency cohort (CRIC). We evaluated the association of time-updated PP with these outcomes, accounting for time-updated confounders using inverse probability weighting. Among 5,621 participants with CKD, every 10-mmHg greater PP was associated with a 6% higher risk of an ASCVD event or death (hazard ratio [HR] = 1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite kidney outcome (HR = 1.17, 95% CI 1.16, 1.18). Greater PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years), but a higher risk of the composite kidney outcome in the oldest age tertile (71-79 years). While wide PP in participants that experienced the primary outcomes was predominantly driven by elevated SBP, PP remained significantly associated with the composite kidney outcome across all ages and with ASCVD events or death in the first age tertile when SBP was added to the Cox regression model. Our findings suggest that the mechanism by which PP is associated with adverse outcomes may differ by age.

Age-related structural remodelling of the coronary circulation.

While it is broadly accepted that ageing is associated with impairment of coronary microvascular function, little is known about the underlying mechanisms. We investigated age-related changes in coronary microvascular structure in patients with stable angina without epicardial coronary stenoses. In an analysis of the IDEAL registry, a total of 165 vessels without coronary stenosis were interrogated with combined pressure/Doppler guidewires. We calculated diastolic microvascular conductance (DMVC) and backward expansion wave (BEW), and compared them between age tertiles. We calculated the prevalence of CMD, defined by reduced coronary flow reserve (CFR), and the prevalence of low BEW and low DMVC in each group. The three study groups were defined as having 37-53, 54-66, and 67-77 years of age, respectively. Oldest (3rd tertile) patients showed lower hyperemic flow velocity (46.7 ± 14.4 vs. 45.1 ± 12.4 vs. 38.4 ± 11.5 cm s-1, p = 0.019), lower DMVC (1.90 ± 0.71 vs. 1.44 ± 0.56 vs. 1.37 ± 0.67 cm s-1 mmHg-1, p < 0.001) and lower BEW intensity (5.9 [2.9-8.4] vs. 4.8 [2.9-6.8] vs. 4.4 [3.4-6.3] × 106 W m-2 s-1, p = 0.094). Older age was independently associated with lower BEW intensity (B: -0.10, 95% confidence interval [CI]: -0.17 to -0.09, p = 0.021) and DMVC (B: -0.25 95% CI: -0.45 to -0.09, p = 0.027). In patients with CFR < 2.5, the prevalence of BEW intensity and DMVC below the 25th percentile increased with age (25.0% vs. 52.0% vs. 72.7%, p = 0.010). Ageing is independently associated with structural microcirculatory remodeling that is reflected in BEW intensity and DMVC measurements, and with an increased prevalence of structural CMD. These results are important to understand non-obstructive mechanisms of myocardial ischemia in the elderly.

Performance of ACR-TIRADS in assessing thyroid nodules does not vary according to patient age.

A few studies have evaluated the performance of the American College of Radiology Thyroid Imaging Reporting And Data System (ACR-TIRADS) in pediatric and elderly patients and found differences between the latter two age groups and middle adulthood. Thus, the present study was undertaken to explore the possible variation of ACR-TIRADS performance across different ages of patients. A retrospective population undergoing thyroidectomy was selected to use histology as the reference standard. Ultrasound images were reviewed, and alignment of ACR-TIRADS with the corresponding histological diagnosis was made afterwards. Results of the age groups were compared. The ACR-TIRADS diagnostic performance was calculated considering the assessment of nodules across risk categories (i.e., from TR1 to TR5), rate of unnecessary FNAC (UN-FNAC), and rate of necessary but non-performed FNAC (NNP-FNAC). Overall, 114 patients with a total of 220 nodules (46 carcinomas) were included. The rate of UN-FNAC was 66.3%, being 93.1% in TR3, 82.1% in TR4, and 31.4% in TR5. There were 15 NNP-FNACs. No significant difference was observed between age groups in terms of sample size, nodule, cancer, and FNAC. The nodule assessment according to ACR-TIRADS categories did not vary across ages. Sensitivity and specificity recorded in three age tertiles were not significantly different. The present study shows that the performance of ACR-TIRADS is not significantly influenced by patient age.

Prior Nonmelanoma Skin Cancer is Associated with Fewer Fractures, More Vitamin D Sufficiency, Greater Bone Mineral Density, and Improved Bone Microarchitecture in Older Adults

BackgroundPrior nonmelanoma skin cancer (NMSC), a biomarker of cumulative lifetime sun exposure, is associated with reduced fracture risk later in life. The mechanism is unknown. MethodsProspective cohort analysis of 1099 community-dwelling adults aged 50-80 years with baseline and 10-year follow-up assessments. Histopathologically-confirmed NMSC diagnosis was established by linkage with the Tasmanian Cancer Registry. Bone mineral density (BMD) and vertebral deformity were quantified by DXA, 25-hydroxyvitamin D (25(OH)D) by radioimmunoassay, bone microarchitecture by high-resolution peripheral quantitative CT, melanin density by spectrophotometry, and skin photosensitivity and clinical fracture by questionnaire. 25(OH)D <50 nmol/L was considered deficient. ResultsParticipants with an NMSC reported prior to baseline were less likely to sustain an incident vertebral deformity over 10 years (RR = 0.74, P = .036). There were similar reductions for other fracture types but these did not reach significance. Prior NMSC was associated with baseline (RR = 1.23, P = .005) and 10-year longitudinal (RR = 5.9, P = .014) vitamin D sufficiency and greater total body BMD (β = 0.021g/cm2, P = .034), but not falls risk or muscle strength. The relationship between prior NMSC and bone microarchitecture was age-dependent (pinteraction < 0.05). In the oldest age tertile, prior NMSC was associated with greater volumetric BMD (β = 57.8-62.6, P = .002-0.01) and less porosity (β = −4.6 to −5.2, P = .002-0.009) at cortical, compact cortical and outer transitional zones. ConclusionsPrior NMSC was associated with fewer incident fractures in community-dwelling older adults. This protective association is most likely mediated by modifiable fracture risk factors associated with an outdoor lifestyle, including 25(OH)D, BMD, and bone microarchitecture.

Association of sex with heart rate variability in atrial fibrillation patients

Abstract Background Sex-specific differences in cardiac autonomic tone have not been thoroughly investigated in patients with atrial fibrillation (AF) but may play a relevant role. Purpose We aimed to investigate cardiac autonomic function of female compared to male AF patients by means of short-term heart rate variability (HRV) analysis. Methods In this cross-sectional analysis, we enrolled 1150 patients from the Swiss-AF cohort study with 5-minute resting ECG recordings in sinus rhythm. We calculated the following HRV parameters: HRV triangular index (HRVI), standard deviation of NN intervals (SDNN), root mean square of successive differences, mean heart rate, power in the high frequency and low frequency range. We fitted linear regression models to analyze the association between gender and HRV variables adjusted for age, intake of betablockers, hypertension, diabetes and heart failure. Results 361 patients (29%) were female (mean age 72.9±7.8 years), 789 (68.6%) were male (mean age 69.8±8.5 years). In the multivariable adjusted models, female sex was associated with significantly lower values of HRVI (β = -0.74; 95% CI -1.44- -0 04, p=0.039) and SDNN (β = 8.95; 95% CI 0.162-17.7, p=0.046). This association persisted in all three age tertiles (&amp;lt;68 years, 68-75 years and ≥ 75 years of age). Conclusions In an elderly AF cohort, female sex is associated with reduced global autonomic activity. Whether this is associated with an adverse prognosis has to be investigated.

Abstract 1065: Age Increases Platelet Aggregation And Alters The Platelet Transcriptome

Introduction: Age is the strongest risk factor for cardiovascular diseases (CVD). Platelets contribute to CVD pathogenesis and may mediate, in part, the association between age and CVD. In this study, we investigated the impact of aging on platelet activity responses and the platelet transcriptome. Hypothesis: Increasing age is associated with increased platelet aggregation and altered transcriptome. Method: Adults ≥ 18 years without CVD, off aspirin or NSAIDS were stratified by age tertiles. Platelet activity was measured by flow cytometry and light transmission aggregometry in response to submaximal agonist stimulation with ADP, AA, collagen, and epinephrine. The association between age and platelet variables were adjusted for sex, race/ethnicity, BMI, hypertension, and diabetes. Differentially expressed transcripts by age were identified using the limma package, adjusted for sex and race/ethnicity. Results: Among 151 participants, median age was 52 years (IQR 38 to 61), 87 (58%) were female, 75 (50%) were non-White, and 27 (18%) were Hispanic. There was no association between platelet count and size with age. There was a significant association between platelet aggregation in response to multiple agonists and age in both unadjusted and adjusted analyses ( Table ). Using a general linear model, we identified 199 platelet transcripts significantly affected by age (P &lt;0.01, 119-positively, 80-negatively). Gene set enrichment analysis demonstrated upregulation of platelet activity pathways (platelet alpha granule [NES = 2.09, q = 0.0008], platelet activation [NES = 1.90, q = 0.002), and platelet aggregation [NES = 1.77, q = 0.03]) with increasing age. Conclusion: Age is independently associated with platelet aggregation in response to submaximal agonist stimulation, a finding supported by the enrichment of platelet activation pathways in the transcriptome. Future studies are needed to elucidate the mechanisms by which age increases platelet aggregation.

Vaccines and Myocardial Injury in Patients Hospitalized for COVID-19 Infection: the CardioCOVID-Gemelli Study.

Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown. To assess the role of vaccines in modifying the risk of myocardial injury in COVID-19. We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit). 1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury. In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.

Abstract TP175: Older Age is Associated With Smaller Ischemic Core Volume and Slower Infarct Progression Despite High Clinical Severity in Anterior Circulation Large Vessel Occlusion Stroke

Background: Older patients with acute stroke due to anterior circulation large vessel occlusion (ACLVO) experience worse clinical outcomes. Fast progressors typically present early with high stroke severity and larger ischemic core volumes. However, the relationship between aging and early infarct growth rate is unknown. We examined the association between older age, baseline ischemic core volumes and fast or slow infarct growth during ACLVO. Methods: Retrospective study of patients with acute ICA or MCA occlusion across two academic centers in 2014-2019. Patients were included if they had baseline CTP or MRI within 24 hours after estimated stroke onset. Infarct growth rate (IGR) was calculated as ischemic core volume (ml) / stroke onset to imaging time (h). Fast or Slow progressor status was defined by IGR ≥ or &lt; 10 ml/h. Univariate comparisons were made across age tertiles. Multivariable linear and logistic regression analysis examined the association of age tertile with ischemic core volume and slow progressor status adjusting for sex, vascular co-morbidities and NIHSS. Results: We included 312 patients (57% female; age tertiles [T1-T3]: 33—66, 67—81, and 82—102). Older age was associated with decreasing ischemic core volume (median [range] ml: T1, 29 [0-253]; T2, 12 [0-406]; T3, 6 [0-244]; p&lt;0.001) and lower IGR (median [range] ml/h: T1, 5.8 [0-153]; T2, 2.6 [0-122.5]; T3, 0.6 [0-248]; p&lt;0.001). The frequency of slow progressors increased with age (N (%): T1, 65/107 (61); T2, 76/105 (72); T3, 78/100 (78); p=0.02). However, baseline NIHSS was numerically higher with older age (median [range]: T1, 16 [1-30]; T2, 17 [2-38]; T3, 18 [1-33]; p=0.22). In multivariable models, age tertile (T3 vs T1) and NIHSS were associated with: 1. ischemic core volume (age coefficient [95% CI], -18.9 [-36.1, -1.7], p=0.03; NIHSS coefficient [95% CI], 3.2[2.3, 4.1], p&lt;0.001); and 2. slow progressor status (age OR 2.63 [1.27, 5.43], p=0.009); NIHSS OR 0.91 [0.87, 0.95], p&lt;0.001). Conclusions: Older age was paradoxically associated with lower baseline core volumes and slow progressor status, despite high stroke severity during acute ACLVO, suggesting older patients may be more vulnerable to even slow infarct growth. Future studies are needed to confirm and extend the findings.

Different sedentary behavior domains present distinct associations with eating-related indicators

BackgroundUnhealthful dietary patterns have been consistently associated with low levels of physical activity (PA), but studies dedicated to sedentary behavior (SB) are scarce, especially in adults. The few studies that investigated the association between SB and dietary patterns focused mostly on specific types of SB, such as TV-watching or screen time. SB can be accumulated in distinct domains (i.e., work, transport, and leisure-time), thus, it is key to investigate in depth the impact that different domains of SB can have on eating-related indicators. We aimed to investigate the associations between different SB domains and eating-related indicators, in a sample of adults.MethodsCross-sectional data from students, teachers, and staff from a Portuguese University was collected in November/2021 through an anonymous online survey. Data analyses were performed using the IBM SPSS software (version 28.0) and included descriptive statistics, partial correlations, and group comparisons using one-way ANOVA. Daily average SB at work/study, transport, and in leisure-time were self-reported and eating-related indicators were measured with several items from the Mediterranean Diet Score. Specific eating-related behaviors reflecting a protective eating pattern (e.g., eating breakfast regularly), and eating behavior traits (e.g., external eating) were also assessed. Body mass index (BMI) was calculated as weight (kg)/height(m)2. The International Physical Activity Questionnaire/Short-Form was used to assess PA.ResultsThe sample included 301 adults (60.1% women), with a mean age of 34.5 years. Overall, leisure-time SB was inversely associated with adherence to the Mediterranean diet (r = -0.20; p < 0.001) and with a protective eating profile (r = -0.31; p < 0.001). Higher transport SB was also related to lower adherence to the Mediterranean diet (r = -0.20; p < 0.001) and to an unhealthier eating profile (r = -0.22; p < 0.001), but no associations were found for work-related SB (p > 0.05). These results persisted after the adjustment for BMI, sex, and self-reported PA. These results were impacted by the age tertile.ConclusionsOur findings suggest that adults with higher levels of SB in leisure-time and transport domains tend to report less healthy eating-related behaviors, irrespective of BMI, sex, and PA level. However, some differences in these associations were found according to the age tertile. This information may assist public health authorities in focusing their efforts in augmenting literacy on SB, namely on how SB can be accumulated via different settings. Furthermore, public health literacy efforts need to extend besides the more known deleterious effects of SB on health (e.g., diabetes, cardiovascular disease), to also include the interplay with eating indicators. Strategies to reduce SB and unhealthy eating should be particularly focused on promoting physically active forms of commuting and reducing SB in the leisure setting.

The Rate of Asystolic Reflex Syncope Is Not Influenced by Age

BackgroundThe head-up tilt test (HUT) and other evidence suggest that the vagal effect on the heart decreases with age. ObjectivesThe main aim of the study was to assess whether this age effect also affects the rate of asystole in spontaneous reflex syncope (RS). MethodWe performed an analysis of pooled individual data from 4 studies that recruited patients ≥40 years of age affected by certain or suspected RS who received an implantable loop recorder (ILR) and reported follow-up data on syncope recurrence. We assessed the presence of asystolic syncope of >3 seconds or nonsyncopal asystole of >6 seconds recorded by ILR and compared the findings to tilt test results on the same patients. ResultsA total of 1,046 patients received ILR because of unexplained syncope. Of these, 201 (19.2%) had a documentation of an asystolic event of 10-second (Q1-Q3: 6- to 15-second) duration. They were subdivided in 3 age tertiles: ≤60 years (n = 64), 61 to 72 years (n = 72), and ≥73 years (n = 65). The rate of asystolic events was similar in the 3 subgroups (50.1%, 50.1%, and 49.2%, respectively; P = 0.99). Conversely, the rate of asystolic syncope induced during HUT (performed in 169 of 201) was greatly age dependent (31.0%, 12.1%, and 11.1% in increasing age tertiles, respectively; P = 0.009). ConclusionsThe rate of the spontaneous asystolic form of RS documented by ILR is constant at any age >40 years. Conversely, the rate of asystolic syncope induced by HUT is higher in younger patients and decreases with age. The contrasting results between spontaneous and tilt-induced events cast doubt on the concept that asystole in RS is less common in older patients.

Characteristics and incidence of cardiac events across spectrum of age in cardiac sarcoidosis

BackgroundClinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. MethodsThis study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. ResultsA total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7–4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74). ConclusionsIn patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups.

The association between menopause and dementia risk

AbstractBackgroundWomen have a higher prevalence of Alzheimer’s disease compared to men. Studies are conflicting as to whether an earlier age of menopause or hysterectomy prior to natural menopause, are associated with an increased risk of cognitive impairment. The goal of this study was to determine whether age of menopause and hysterectomy are associated with incident dementia in a group of older, community‐dwelling women.MethodFemale participants from three ongoing Rush cohorts, the Rush Memory and Aging Project, the Religious Orders Study, and the Minority Aging Research Study were included (total n = 3122, mean age = 77 years at baseline, SD = 7.8). Annual clinical assessments allowed for dementia status categorization, based on detailed neuropsychological testing and clinical judgment, using the NINDS‐ADRDA criteria. Age at menopause and hysterectomy status was based on self‐report at baseline. Data on ovarian preservation or removal at time of surgery was not available. Age of menopause was categorized into tertiles (&lt;45, 45‐50, &gt;50). Risk of dementia, with age at dementia diagnosis as the outcome, was evaluated using Cox proportional regression models adjusting for race, early‐life socioeconomic status, education, diabetes, and smoking status.ResultAt the time of these analyses, women were followed for an average of 8.3 years (SD = 5.6). Women in the earliest tertile of menopause age were less likely to be white, more likely to report having diabetes, and have longer hormone therapy use (p&lt;0.01). In fully adjusted models, women with menopause at age 45‐50 (HR 0.80, 95% CI 0.67‐0.96) and age &gt;50 (HR 0.74, 95% CI 0.62‐0.90) had a lower risk of dementia compared to women with menopause at age &lt;45. Hysterectomy prior to natural menopause was not associated with an elevated risk of dementia (HR = 1.01, 95% CI 0.87‐1.19).ConclusionIn a group of older women, earlier age at menopause but not hysterectomy was associated with an elevated risk of dementia. Future research will determine whether these associations differ by race or ethnicity and the factors that may contribute to such differences.Funding: P30‐AG072975, R01‐AG17917, R01‐AG22081

The influence of widowhood on amyloid positivity status in cognitively normal older adults

AbstractBackgroundWidowhood and associated spousal bereavement is a life event that may lead to stress, loneliness, and depression. Previous research found associations between widowhood and an elevated risk of dementia. However, no direct relationship has been evidenced between widowhood and beta‐amyloid (Aβ) pathology, which is a hallmark of Alzheimer’s disease. Additionally, little is known about whether particular demographic or background factors might contribute to potential influences of widowhood on Aβ levels in older adults. Our objective was to evaluate the relationship between widowhood and Aβ positivity status in older adults, and to determine whether subgroups based on age, gender, educational attainment, or APOE ε4 status are driving effects.MethodCognitively normal (CN) subjects (n = 182) who were either widowed (including widows and widowers) or married from the Alzheimer’s Disease Neuroimaging Initiative were included in this study that underwent [18F]Florbetapir PET imaging on the baseline study visit. Multivariable logistic regression interrogated associations between widowhood status and Aβ positivity classification based on a global standardised uptake value ratio threshold of 1.11. This analysis included age, gender, APOE ε4 allele possession, education, and MMSE score as covariates. Regressions were also run in subgroups of CN subjects based on gender (male vs. female), APOE ε4 allele possession (carriers vs. non‐carriers), age (youngest, middle, oldest tertiles), and education (at least an undergraduate degree vs. no undergraduate degree).ResultIn CN subjects, there was overall no significant association between widowhood status and Aβ positivity (p = 0.114). When examining subgroups, widowhood was significantly associated with an increased risk of Aβ positivity in CN individuals with an undergraduate degree or higher (p = 0.025) or in the oldest age tertile (ages ranging from 76.3 to 89) (p = 0.024).ConclusionFindings from this cross‐sectional study indicated that a positive relationship between widowhood and in vivo Aβ neuropathology measured by PET exists specifically in those that are highly educated or undergoing advanced ageing. Whereas cognitive reserve is often hypothesised to mediate links between social isolation, depression and dementia risk, these results suggest that there may also be a direct effect on Alzheimer’s disease neuropathology.

Abstract 12444: Pulse Pressure and Cardiovascular and Renal Outcomes by Age in the Chronic Renal Insufficiency Cohort

Pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). While PP is known to widen with age, it is less clear what other clinical factors affect PP and whether the risks associated with wide PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with development of 1) atherosclerotic cardiovascular disease (ASCVD) events (congestive heart failure hospitalization, myocardial infarction, stroke and peripheral artery disease) or death and 2) 50% reduction in estimated glomerular filtration rate (eGFR) or ESKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. In sensitivity analyses, we evaluated the association of time-updated PP with these outcomes, accounting for potential time-updated confounders using inverse probability of treatment weighting. We evaluated for effect modification by age (divided into tertiles), apparent treatment-resistant hypertension (HTN), baseline diabetes mellitus (DM) status, baseline CKD stage and baseline cardiovascular disease (CVD). Among 5,621 participants with CKD followed for ~5.4 years, mean PP was 57±19 mmHg, 1,396 (25%) had an ASCVD event, 1,186 (21%) died and 1,783 (32%) participants experienced the composite renal outcome. Every 10 mm Hg wider PP was associated with 6% higher risk of an ASCVD event or death (time-updated adjusted hazard ratio [HR]=1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite renal outcome (time-updated adjusted HR=1.17, 95% CI 1.16, 1.18). Wider PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years; Figure 1A ), but a higher risk of the composite renal outcome in the oldest age tertile (71-79 years; Figure 1B ), suggesting PP may be associated with different pathophysiology across ages.

Impact of age on pre-procedural TIMI flow in STEMI patients undergoing primary percutaneous coronary intervention.

Advanced age is a major determinant of impaired prognosis among patients with ST-segment elevation myocardial infarction (STEMI). However, the mechanisms associated with suboptimal reperfusion and enhanced complications are still largely undefined. The aim of the present study was to assess the impact of age on the angiographic findings and the procedural results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. A consecutive cohort of patients admitted for STEMI treated with pPCI were included. Infarct-related artery (IRA) patency was defined for preprocedural TIMI flow 3. We included 520 patients, divided according to age tertiles (<61; 61-72; ≥73). Elderly patients were more often females, with hypertension, renal failure, prior myocardial infarction or PCI, with lower rates of smoking history, haemoglobin, leukocytes and cholesterol (P < 0.001), lower ejection fraction (P = 0.02), higher use of renin angiotensin system inhibitors, statins, ASA, calcium antagonists, diuretics and beta blockers. At angiography, for the IRA, percentage of thrombus (P = 0.02) and stenosis (P = 0.01), direct stenting (P = 0.02) and glycoprotein IIb-IIIa inhibitors (P = 0.04) inversely related with age, but for higher restenosis (P = 0.04). IRA patency was more common in patients aged ≥73 years (27.9% vs. 32.3% vs. 41.1%, P = 0.01). The impact of age on preprocedural TIMI flow was confirmed at multivariate analysis [adjusted odds ratio (95% confidence interval) = 0.68 (0.47-0.98), P = 0.04]. The present study shows that among STEMI patients undergoing primary PCI, more advanced age represents an independent predictor of preprocedural IRA patency. Future studies will define the implications on procedural results and long-term prognosis.

ESTIMATED VERSUS MEASURED AORTIC STIFFNESS IN DIALYSIS POPULATION: IMPLICATIONS OF SEX, AGE AND DIABETES

Objective: Aortic stiffness is measured through determination of carotid-femoral pulse wave velocity(cfPWV). More recently, authors have proposed to estimate PWV (ePWV) with age and brachial mean blood pressure (MBP) using an equation for the normal population and another for subjects with cardiovascular risk factors. However, patients with end-stage kidney disease are at extremely high risk of cardiovascular disease and have an altered circulatory system due to no perfusion of the kidneys. Therefore, the aim of this study was 1)examine the reliability of the ePWV as compared to measured cfPWV, and 2)examine if sex, age and diabetes have an impact on the relationship between ePWV and cfPWV in this population. Design and method: This is a cross-sectional study of 317 adults treated by chronic hemodialysis(n = 252) or peritoneal dialysis(n = 65). cfPWV was measured using second derivative algorithm through simultaneous recording of carotid and femoral arteries in triplicates(CompliorSP) using 80% of the direct distance between the carotid and femoral arteries. ePWV was calculated using the formula for subjects with cardiovascular risk factors from the Reference Values for Arterial Stiffness Collaboration. Results: In 317 patients(68%men), with a mean age of 65 ± 15 years, 43% had diabetes, 91% had hypertension and 52% had cardiovascular disease. MBP, cfPWV and the difference between ePWV and cfPWV(↗PWV) were respectively 92 ± 17mmHg, 10.8 ± 3.2m/s and 0.36(-5.87 – 11.84) in the overall group. Male sex, first and second age tertiles, and diabetes were associated with a negative ↗PWV. ePWV underestimated cfPWV in men (-0.80, 95%CI: -1.17 – -0.43, p &lt; 0.001), in patients from the first (18-60 years)(-0.64, 95%CI: -0.94 – -0.32), p &lt; 0.001) and second (60 - 73 years)(-0.50, 95%CI: -1.01 – 0.01,p = 0.053) tertiles of age, and in patients with diabetes(-1.08, 95%CI: -1.55 – -0.60, p &lt; 0.001). ePWV was relatively accurate to estimated cfPWV in women (0.28, 95%CI: -0.09 – 0.66, p = 0.132) and in patients from the last age tertile(73 - 89 years)(0.05, 95%CI: -0.51 – 0.66,p = 0.866). Conclusions: These findings suggest that sex, age tertiles and diabetes impact the relationship between ePWV and cfPWV in our cohort of patients on dialysis; therefore the formula used to estimate PWV may benefit from better integrating these determinants for a more accurate ePWV.

Subcutaneous ICD therapy results in a similar quality of life compared with transvenous ICD therapy during both short- and long-term follow-up

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific Medical device company St. Paul, Minnesota, USA Introduction The PRAETORIAN trial showed that the subcutaneous implantable cardioverter defibrillator (S-ICD) is noninferior to the transvenous ICD (TV-ICD) with respect to device-related complications and inappropriate shocks in a conventional ICD population. It is unknown whether there is a difference in quality of life (QoL) between the two patient groups. The generator size and implant location differ between both devices. This may cause a variation in mental health status and pain perception between treatment arms, in particular in older patients, patients with low BMI, and females. Purpose This prespecified analysis of the PRAETORIAN trial compares the impact of the S-ICD and TV-ICD on QoL. Methods In the PRAETORIAN trial, 849 patients were randomised to S-ICD (n=426) or TV-ICD (n=423) therapy. QoL was prospectively measured at baseline, discharge and 12 and 30 months after ICD implant, by measuring cardiac-specific physical functioning with the Duke Activity Status Index (DASI) and psychological and physical well-being with the 36-Item Short Form Health Survey (SF-36, divided in 8 subscales). Patients who completed the questionnaires at baseline were included in this analysis. At each time point the mean change in score from baseline was calculated. Subgroups were made based on age (tertiles, &amp;lt; 58, 58-67 and &amp;gt;67 years), BMI categories (&amp;lt;25, 25-30, and ≥30 kg/m2) and sex. In these subgroups, we only looked at differences in pain and mental health between arms. Treatment effects, 95% CIs and interactions were calculated by regression models. Results A total of 823/849 patients completed the QoL questionnaires at baseline. Questionnaires were also completed by these patients at discharge (92%), 12 months (85%) and 30 months (69%). There was no difference in QoL between the arms at any time point (p&amp;gt;0.05, figure). Age, BMI and sex were not associated with a difference between the arms in SF-36 subscale bodily pain (p=0.73, 0.72 and 0.92 respectively), or SF-36 subscale mental health (p=0.15, 0.39 and 0.76) at 30 months. Similar results were seen at discharge and 12 months. Conclusion There were no differences in QoL between S-ICD and TV-ICD treatment in the first 30 months after implant. In addition, no differences in pain and mental health were seen in older patients, patients with low BMI and females. These results confirm that the S-ICD is a good alternative for the TV-ICD.

129Xe MRI Ventilation Defects in Asthma: What is the Upper Limit of Normal and Minimal Clinically Important Difference?

The minimal clinically important difference (MCID) and upper limit of normal (ULN) for MRI ventilation defect percent (VDP) were previously reported for hyperpolarized 3He gas MRI. Hyperpolarized 129Xe VDP is more sensitive to airway dysfunction than 3He, therefore the objective of this study was to determine the ULN and MCID for 129Xe MRI VDP in healthy and asthma participants. We retrospectively evaluated healthy and asthma participants who underwent spirometry and 129XeMRI on a single visit; participants with asthma completed the asthma control questionnaire (ACQ-7). The MCID was estimated using distribution- (smallest detectable difference [SDD]) and anchor-based (ACQ-7) methods. Two observers measured VDP (semiautomated k-means-cluster segmentation algorithm) in 10 participants with asthma, five-times each in random order, to determine SDD. The ULN was estimated based on the 95% confidence interval of the relationships between VDP and age. Mean VDP was 1.6 ± 1.2% for healthy (n=27) and 13.7 ± 12.9% for asthma participants (n=55). ACQ-7 and VDP were correlated (r=.37, p=.006; VDP=3.5·ACQ+4.9). The anchor-based MCID was 1.75% while the mean SDD and distribution-based MCID was 2.25%. VDP was correlated with age for healthy participants (p=.56, p =.003; VDP=.04·Age-.01). The ULN for all healthy participants was 2.0%. By age tertiles, the ULN was 1.3% ages 18-39 years, 2.5% for 40-59 years and 3.8% for 60-79 years. The 129Xe MRI VDP MCID was estimated in participants with asthma; the ULN was estimated in healthy participants across a range of ages, both of which provide a way to interpret VDP measurements in clinical investigations.

Factors Affecting the Vitamin C Dose-Concentration Relationship: Implications for Global Vitamin C Dietary Recommendations

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to investigate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations, and the possible extent of these additional requirements. The final cohort comprised 2828 non-supplementing adult males and females (aged 18-80+ years) with both vitamin C serum concentrations and dietary intake data available. The data were subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: ≤1.35, 1.36-3.0, >3.0), weight tertiles (<72, 72-91, >91 kg), BMI tertiles (<26, 26-32, >32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach 'adequate' serum vitamin C concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heavier weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes > 75 mg/day, at intakes < 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population should consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach comparable vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.